Thèse soutenue

Analyse de la conformation locale des structures protéiques : irrégularités des feuillets béta, modifications post-traductionnelles et flexibilité
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Auteur / Autrice : Pierrick Craveur
Direction : Alexandre de Brevern
Type : Thèse de doctorat
Discipline(s) : [Bioinformatique, Analyse de génome et modélisation]
Date : Soutenance en 2014
Etablissement(s) : Paris 7

Résumé

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I based my work on a representation of proteins developed in the laboratory: the structural alphabet of Protein Blocks (PBs). This alphabet is used to describe and study the local conformations of protein structures. With this representation I have firstly studied the structural irregularities observed in the 13 sheets, the β-bulges. They are described in the literature as conserved among protein families and impacting the structure and function of proteins. I tried to answer the question: are the β-bulges actually conserved within homologs folds? In a second time, I studied the post-translational modifications (PTMs), which essentially correspond to very different modifications of the protein residues. These PTMs are increasingly studied in the structural context, and their impact on the flexibility is more pointed. I have developed a database that curates the structures containing annotated modifications as PTMs. With this data I have tried to answer the question: Did the PTMs affect protein structure? This effect is global or local in protein structure? Finally in the last part of my thesis, I studied the correlation between local conformations and flexibility of the polypeptide backbone. Through numerous molecular dynamics simulations, I have attempted to quantify this correlation, systematically, and in view of the presence of β-bulges and PTMs sites. These works bring a new look on the prediction method developed in the laboratory flexibility.